351 Predictors of HIV-specific Immune Responses in Chronically HIV-infected Subjects on Antiretroviral Therapy A. Siddique*1, E. Dragileva1, K. E. Hartman1, J. Campagna1, D. W. Cherng2, M. Dondero3, L. Peiperl4, F. Valentine5, S. A. Kalams6 1Partners AIDS Res Ctr and Massachusetts Gen Hosp, Boston, MA; 2Statistical and Data Analysis Ctr, Boston, MA; 3AACTG Operations Ctr, Silver Spring, MD; 4Univ of California at San Francisco, AIDS Clin Trials Unit; 5New York Univ Med Ctr; and 6Partners AIDS Res Ctr and Vanderbilt Univ Med Ctr, Nashville, TN
Background: The identification and longitudinal follow-up of cell-mediated immune responses to HIV proteins will be important for evaluating the effect of immunotherapeutic vaccines. Some current protocols exclude subjects with low CD4 T-cell nadirs out of fear that these subjects will not be able to respond to vaccine candidates designed to augment HIV-specific cell-mediated immune responses. We, therefore, set out to determine the breadth and specificity of HIV-1 specific CTL and Th responses in a cohort of patients entering a clinical trial whose viral replication is suppressed with HAART.
Method:All subjects had undetectable viral loads (< 50 copies/ml) on HAART on study entry, and these subjects were stratified based on the length of time they were completely suppressed (either > 15 months [mos] or between 3 and 15 mos of suppression). We tested these subjects with previously defined HLA optimal CTL peptides and pools of peptides from the HIV gag protein. Despite prolonged anti-retroviral therapy and viral loads of < 50 copies, virtually all subjects tested had detectable CTL responses (n = 30). The mean number of peptides tested, representing optimal CTL epitopes, was 22.7 and the mean number of recognized epitopes was 5.3.
Results:Our preliminary results demonstrate a positive correlation between baseline CD4 counts and the magnitude of CTL responses as measured by ELISpot (R = 0.6, p = 0.03). Although there was a trend in the relationship between the CD4+ T-cell nadir and the magnitude of HIV specific CTL responses, this association did not achieve statistical significance (R = 0.53, p = 0.07). In contrast, CD4 T-cell nadirs did correlate with lymphoproliferative responses (R = 0.57, p = 0.03).
Conclusions: Although we await confirmation with further data analysis, we conclude that both nadir CD4+ T-cell numbers or the CD4+ T-cell numbers at entry are good predictors of the magnitude of HIV-specific cell-mediated immune responses, and the associations may depend on the immune response being measured. Future immunotherapy studies may not necessarily have to exclude subjects with low CD4+ T-cell nadirs.
